Histological quantitation of tumour angiogenesis

Abstract

Tumours establish their blood supply via a number of processes in addition to angiogenesis. These include vasculogenesis, vascular remodelling, intussusception and possibly vascular mimicry in certain tumours. The mainstay of the assessment of tumour vascularity has been counting the number of immunohistochemically identified microvessels in vascular hot spots. Nevertheless, several other techniques are available, including Chalkley counting, vascular grade and the use of image analysis systems. Angiogenic activity can furthermore be assessed in histological samples by measuring the molecules involved in the establishment of the tumour vasculature, including angiogenic growth factors and their receptors, cell adhesion molecules, proteases and markers of activated, proliferating, cytokine stimulated or angiogenic vessels, such as CD105. Measuring the maturity of vessels may give an indication of the proportion of the tumour vasculature that is functional. Other reagents that can identify hypoxia-activated pathways are also being developed. The histological assessment of tumour vascularity is mainly used in the research setting but may also have applications in the clinic if appropriate methodology and trained observers perform the studies. Gene arrays may be able to provide an angiogenesis profile. Continued study into the processes involved in generating a tumour blood supply is likely to identify new markers that may be more accurate measures.